Considerable evidence indicates that the metabolic activity of folate is determined by the length of the gamma-glutamyl side chain, as well as by one-carbon substituents. It is also known that a large portion of dietary folate is in the polyglutamate form. We propose to continue our studies on factors involved in the cellular uptake of folate, whether in the form of monoglutamate or polyglutamate. We also propose to study the metabolic effects on events in the cell-cycle of enzymes such as conjugase, of conjugase inhibitors, and folate binders.